Complement is involved in many immune and immunopathological reactions including B cell differentiation into antibody producing plasma cells, B cell mediated cytotoxicity, macrophage activation, immune adherence and release of proteolytic lysosomal enzymes such as collagenase from phagocytes and stimulation of osteoclasts via prostaglandin induction. We recently discovered that functional complement components are continuously flowing into the oral cavity via the gingival crevicular fluid of patients with periodontal disease. Thus, persistent contact between oral salivary secretions and fresh crevicular complement occurs at the gingival margin. With the exception of our initial work, which is reviewed in this application, no sound information is available on the nature of saliva-complement interactions. An in vitro study of saliva-complement interactions is of paramount importance if we are to understand the nature of complement's important role in oral health and disease. Thus, the primary objective of this proposal is to examine in vitro the interaction between salivary secretions and the complement system. In preliminary studies described in this application we have found that salivary secretions contain several factors which affect the function of the complement system. It is possible that some of the salivary factors from the glandular secretions may act to prevent the inflammatory nature of continued complement activation. We intend to examine closely the complex nature of the interactions bewteen saliva and the complement system; to isolate and identify salivary substances which affect complement activity; and thereby develop the beginning of a molecular understanding of saliva-complement interactions.